2024
TET3-overexpressing macrophages promote endometriosis
Lv H, Liu B, Dai Y, Li F, Bellone S, Zhou Y, Mamillapalli R, Zhao D, Venkatachalapathy M, Hu Y, Carmichael G, Li D, Taylor H, Huang Y. TET3-overexpressing macrophages promote endometriosis. Journal Of Clinical Investigation 2024, 134: e181839. PMID: 39141428, PMCID: PMC11527447, DOI: 10.1172/jci181839.Peer-Reviewed Original ResearchDisease-associated macrophagesTET3 overexpressionHuman endometriosis lesionsPathophysiology of endometriosisPro-inflammatory cytokine productionChronic inflammatory diseaseReproductive age womenEndometriosis lesionsE3 ubiquitin ligasePathogenic macrophagesCytokine productionEndometriosisInflammatory diseasesTET3 knockdownEndometriosis progressionPathogenic contributorsLet-7 miRNA expressionAge womenMacrophagesMouse macrophagesTherapeutic targetUbiquitin ligaseTET3MiceDiseaseA circadian clock output functions independently of phyB to sustain daytime PIF3 degradation
Liu W, Lowrey H, Xu A, Leung C, Adamchek C, He J, Du J, Chen M, Gendron J. A circadian clock output functions independently of phyB to sustain daytime PIF3 degradation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2408322121. PMID: 39163340, PMCID: PMC11363348, DOI: 10.1073/pnas.2408322121.Peer-Reviewed Original ResearchConceptsPhytochrome-interacting factorsF-boxRed-light photoreceptor phytochrome BPhotoreceptor phytochrome BCircadian clock outputE3 ubiquitin ligaseDownstream biological processesPhyB signalingGrowth-regulating mechanismsTranscriptional connectionsPhytochrome BClock's roleRhythmic transcriptionUbiquitin ligaseClock regulationGenetic evidenceMonochromatic red lightProtein stabilityCircadian clockPhyBBiological processesPlant growthClock outputCircadian expressionRegulation mechanismHyd/UBR5 defines a tumor suppressor pathway that links Polycomb repressive complex to regulated protein degradation in tissue growth control and tumorigenesis
Wen P, Lei H, Deng H, Deng S, Tirado C, Wang M, Mu P, Zheng Y, Pan D. Hyd/UBR5 defines a tumor suppressor pathway that links Polycomb repressive complex to regulated protein degradation in tissue growth control and tumorigenesis. Genes & Development 2024, 38: 675-691. PMID: 39137945, PMCID: PMC11368183, DOI: 10.1101/gad.351856.124.Peer-Reviewed Original ResearchConceptsPolycomb Repressive Complex1Tumor suppressor pathwayTissue growth controlSuppressor pathwayProtein degradationZinc finger genesGrowth controlUbiquitin-mediated degradationE3 ubiquitin ligasePolycomb repressive complexesProtein degradation pathwaysTumor suppressor geneHyperplastic discsFinger genesMammalian homologSubstrate adaptorRepressive complexesUbiquitin ligaseEmbryonic segmentationProtein complexesModel organismsHuman geneticsUpstream regulatorSuppressor geneProstate cancer tumorigenesisRBX1-CRLs Promote Perinatal Heart Development by Regulating Hippo-YAP Signaling
Zambrano-Carrasco J, Wang W, Ayala J, Sibley J, Carruth J, Jiao K, Li J, Su H. RBX1-CRLs Promote Perinatal Heart Development by Regulating Hippo-YAP Signaling. Physiology 2024, 39: 963. DOI: 10.1152/physiol.2024.39.s1.963.Peer-Reviewed Original ResearchCullin-RING E3 ubiquitin ligasesCongenital heart diseaseCardiomyocyte proliferationCardiac developmentNuclear translocation of YAPTransfer of ubiquitinMulti-subunit complexesE3 ubiquitin ligasePerinatal heart developmentTranslocation of YAPHippo-YAP signalingInactivation of YAPImpaired nuclear translocationCo-transcription factorCardiac malformationsMyocardial hypoplasiaPeripheral edemaAdaptor proteinCKO heartsCullin-RINGLittermate controlsProtein substratesEdU incorporation assayHippo kinasesProtein homeostasisEmerging Roles of Cullin-RING Ubiquitin Ligases in Cardiac Development
Zambrano-Carrasco J, Zou J, Wang W, Sun X, Li J, Su H. Emerging Roles of Cullin-RING Ubiquitin Ligases in Cardiac Development. Cells 2024, 13: 235. PMID: 38334627, PMCID: PMC10854628, DOI: 10.3390/cells13030235.Peer-Reviewed Original ResearchConceptsUbiquitin ligaseFamily of ubiquitin ligasesCullin-RING ubiquitin ligasesE3 ubiquitin ligaseRegulation of heart developmentPost-translational mechanismsHeart developmentRegulation of cardiac morphogenesisCongenital heart diseaseCardiac developmental processesSpatiotemporally regulated processCullin-RINGDevelopment of innovative therapiesEpigenetic regulationIntracellular proteinsLigaseMolecular mechanismsDevelopmental processesHeart failureInnovative therapiesCardiac developmentCardiac morphogenesisPostnatal stagesHeart diseaseOrchestrated process
2023
Atorvastatin rescues vascular endothelial injury in hypertension by WWP2-mediated ubiquitination and degradation of ATP5A
Yin Z, You S, Zhang S, Zhang L, Wu B, Huang X, Lu S, Cao L, Zhang Y, Li D, Zhang X, Liu J, Sun Y, Zhang N. Atorvastatin rescues vascular endothelial injury in hypertension by WWP2-mediated ubiquitination and degradation of ATP5A. Biomedicine & Pharmacotherapy 2023, 166: 115228. PMID: 37557013, DOI: 10.1016/j.biopha.2023.115228.Peer-Reviewed Original ResearchConceptsMitochondrial pathway of apoptosisRegulate protein ubiquitinationPathway of apoptosisE3 ubiquitin ligaseVascular endothelial injuryDeath of vascular endothelial cellsEndothelial injuryMitochondrial pathwayUbiquitin ligaseWWP2 overexpressionProteasome pathwayProtein ubiquitinationBcl-2/BaxBiological processesWWP2Vascular endotheliumATP5ALipid-lowering drugsUbiquitinEffect of atorvastatinImproving vascular endothelial functionVascular endothelial functionDamaged vascular endotheliumVascular endothelial cellsMechanism of atorvastatin
2022
PROTACs: past, present and future
Li K, Crews CM. PROTACs: past, present and future. Chemical Society Reviews 2022, 51: 5214-5236. PMID: 35671157, PMCID: PMC10237031, DOI: 10.1039/d2cs00193d.Peer-Reviewed Original ResearchConceptsProtein of interestProteolysis-targeting chimerasUbiquitin-proteasome systemE3 ubiquitin ligaseSmall molecule inhibitorsUbiquitin ligaseNonenzymatic functionProtein degradationHeterobifunctional moleculesDrug resistance mechanismsMolecule inhibitorsSubsequent degradationUbiquitinationLigasePromising therapeuticsProteinChimerasPotential toxicityDegradationMechanism
2020
Gαs (GNAS) suppression of the p53 genomic‐stability checkpoint unleashes RAS‐driven oncogenesis
Steffen D, Tiriac H, Valera J, Amornphimoltham P, Kim W, Taylor S, Hunter T, Tamayo P, Gutkind J. Gαs (GNAS) suppression of the p53 genomic‐stability checkpoint unleashes RAS‐driven oncogenesis. The FASEB Journal 2020, 34: 1-1. DOI: 10.1096/fasebj.2020.34.s1.04604.Peer-Reviewed Original ResearchTrp53 tumor suppressor geneCooperation of rasMDM2-mediated p53 ubiquitinationHuman intestinal organoid modelP53 E3 ubiquitin ligaseSquamous cell carcinomaIn vitro ubiquitination assayP53 protein accumulationChemical carcinogen DMBASkin of adult miceTumor suppressor genePhosphorylation of Mdm2Control genome stabilityE3 ubiquitin ligaseRAS mutant tumorsRas-driven oncogenesisCarcinogenesis in vivoSubstrate of PKAConstitutively activating mutationAppendix cancerPan-cancer analysisActivation of signalingPatient sequencing dataBenign tumorsCell carcinoma
2017
Infection-derived lipids elicit an immune deficiency circuit in arthropods
Shaw DK, Wang X, Brown LJ, Chávez AS, Reif KE, Smith AA, Scott AJ, McClure EE, Boradia VM, Hammond HL, Sundberg EJ, Snyder GA, Liu L, DePonte K, Villar M, Ueti MW, de la Fuente J, Ernst RK, Pal U, Fikrig E, Pedra JH. Infection-derived lipids elicit an immune deficiency circuit in arthropods. Nature Communications 2017, 8: 14401. PMID: 28195158, PMCID: PMC5316886, DOI: 10.1038/ncomms14401.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnaplasma marginaleAnaplasma phagocytophilumAnimalsArthropodsBorrelia burgdorferiCarrier ProteinsDisease Models, AnimalDrosophila melanogasterDrosophila ProteinsEscherichia coliFas-Associated Death Domain ProteinGene SilencingHEK293 CellsHumansImmunologic Deficiency SyndromesIxodesLipidsLyme DiseasePhosphatidylglycerolsRecombinant ProteinsRNA, Small InterferingSignal TransductionTranscription FactorsUbiquitin-Conjugating EnzymesUbiquitin-Protein LigasesX-Linked Inhibitor of Apoptosis ProteinConceptsAdaptor molecule FasImmune deficiency (IMD) pathwayPeptidoglycan recognition proteinsE3 ubiquitin ligaseLyme disease spirochete Borrelia burgdorferiIMD pathwayGram-negative bacteriaRecognition proteinsUbiquitin ligaseDeath domainApoptosis proteinDistinct bacteriaBiochemical interactionsMolecule FasSpirochete Borrelia burgdorferiReceptor networkA. marginaleProteinAnaplasma phagocytophilumBacteriaPathwayBorrelia burgdorferiInsectsLipidsArthropods
2016
Loss of Cbl-PI3K interaction modulates the periosteal response to fracture by enhancing osteogenic commitment and differentiation
Scanlon V, Walia B, Yu J, Hansen M, Drissi H, Maye P, Sanjay A. Loss of Cbl-PI3K interaction modulates the periosteal response to fracture by enhancing osteogenic commitment and differentiation. Bone 2016, 95: 124-135. PMID: 27884787, PMCID: PMC5819877, DOI: 10.1016/j.bone.2016.11.020.Peer-Reviewed Original ResearchMeSH KeywordsAlkaline PhosphataseAnimalsBiomarkersCell CountCell DifferentiationCell LineageCell NucleusCell ProliferationFracture HealingFractures, BoneMesodermMice, Inbred C57BLMutationOsteogenesisPeriosteumPhosphatidylinositol 3-KinasePhosphorylationProtein BindingProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-cblSp7 Transcription FactorUp-RegulationConceptsCbl-PI3K interactionUbiquitin ligase functionMultipotent skeletal progenitorsPeriosteal cellsPI3KMajor adaptor proteinP85 regulatory subunitTranscriptional target genesE3 ubiquitin ligaseOsteogenic differentiationPhosphatidylinositol-3 kinasePI3K regulationMajor signaling proteinsK interactionPI3K activityPeriosteal thickeningLipid kinasesP85 subunitSkeletal progenitorsAdaptor proteinRegulatory subunitLigase functionSignaling proteinsUbiquitin ligaseNuclear localization
2013
dBre1/dSet1-dependent pathway for histone H3K4 trimethylation has essential roles in controlling germline stem cell maintenance and germ cell differentiation in the Drosophila ovary
Xuan T, Xin T, He J, Tan J, Gao Y, Feng S, He L, Zhao G, Li M. dBre1/dSet1-dependent pathway for histone H3K4 trimethylation has essential roles in controlling germline stem cell maintenance and germ cell differentiation in the Drosophila ovary. Developmental Biology 2013, 379: 167-181. PMID: 23624310, DOI: 10.1016/j.ydbio.2013.04.015.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosis Regulatory ProteinsCell DifferentiationDNA PrimersDrosophila melanogasterDrosophila ProteinsEpigenesis, GeneticFemaleGerm CellsHistone MethyltransferasesHistone-Lysine N-MethyltransferaseHistonesMethylationMicroscopy, FluorescenceOvaryReal-Time Polymerase Chain ReactionRNA InterferenceStatistics, NonparametricStem Cell NicheStem CellsUbiquitin-Protein LigasesConceptsGermline stem cellsGerm cell differentiationStem cell nicheCell differentiationDrosophila ovaryGSC maintenanceDrosophila ovarian germline stem cellsCell nicheGermline stem cell maintenanceOvarian germline stem cellsCell fate regulationStem cell maintenanceHistone H3K4 trimethylationE3 ubiquitin ligaseStem cellsSingle germ cellEscort cellsGSC lossGSC regulationChromatin remodelingMutant ovariesH3K4 methylationHistone modificationsFate regulationH3K4 trimethylationGenomic Analysis of Non-NF2 Meningiomas Reveals Mutations in TRAF7, KLF4, AKT1, and SMO
Clark VE, Erson-Omay EZ, Serin A, Yin J, Cotney J, Özduman K, Avşar T, Li J, Murray PB, Henegariu O, Yilmaz S, Günel JM, Carrión-Grant G, Yılmaz B, Grady C, Tanrıkulu B, Bakırcıoğlu M, Kaymakçalan H, Caglayan AO, Sencar L, Ceyhun E, Atik AF, Bayri Y, Bai H, Kolb LE, Hebert RM, Omay SB, Mishra-Gorur K, Choi M, Overton JD, Holland EC, Mane S, State MW, Bilgüvar K, Baehring JM, Gutin PH, Piepmeier JM, Vortmeyer A, Brennan CW, Pamir MN, Kılıç T, Lifton RP, Noonan JP, Yasuno K, Günel M. Genomic Analysis of Non-NF2 Meningiomas Reveals Mutations in TRAF7, KLF4, AKT1, and SMO. Science 2013, 339: 1077-1080. PMID: 23348505, PMCID: PMC4808587, DOI: 10.1126/science.1233009.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBrain NeoplasmsChromosomes, Human, Pair 22DNA Mutational AnalysisFemaleGenes, Neurofibromatosis 2Genomic InstabilityGenomicsHumansKruppel-Like Factor 4Kruppel-Like Transcription FactorsMaleMeningeal NeoplasmsMeningiomaMiddle AgedMutationNeoplasm GradingProto-Oncogene Proteins c-aktReceptors, G-Protein-CoupledSmoothened ReceptorTumor Necrosis Factor Receptor-Associated Peptides and Proteins
2012
The E6AP E3 ubiquitin ligase regulates the cellular response to oxidative stress
Wolyniec K, Levav-Cohen Y, Jiang Y, Haupt S, Haupt Y. The E6AP E3 ubiquitin ligase regulates the cellular response to oxidative stress. Oncogene 2012, 32: 3510-3519. PMID: 22986523, DOI: 10.1038/onc.2012.365.Peer-Reviewed Original ResearchConceptsE3 ubiquitin ligaseReactive oxygen speciesUbiquitin ligaseStress responseCellular responsesE6AP expressionStress conditionsImportant stress conditionsCell growthCellular stress responseAppropriate cellular responsesOxidative stress responseSpecific stress conditionsOxidative stressIntracellular reactive oxygen speciesOncogenic RasCellular senescenceGrowth-suppressive effectsOxidative DNA damageApoptotic responseNovel roleCell deathImportant regulatorE6APDNA damage
2011
E6AP is required for replicative and oncogene-induced senescence in mouse embryo fibroblasts
Levav-Cohen Y, Wolyniec K, Alsheich-Bartok O, Chan A, Woods S, Jiang Y, Haupt S, Haupt Y. E6AP is required for replicative and oncogene-induced senescence in mouse embryo fibroblasts. Oncogene 2011, 31: 2199-2209. PMID: 21927031, DOI: 10.1038/onc.2011.402.Peer-Reviewed Original ResearchConceptsMouse embryo fibroblastsOncogene-induced senescenceCellular responsesEmbryo fibroblastsCellular stress responseRas-induced senescenceE3 ubiquitin ligaseStress-induced accumulationRole of E6APUbiquitin ligaseProtein regulatorsTissue homeostasisReplicative senescenceCellular senescenceCell cycleStress responseImportant regulatorSenescenceStress conditionsE6APIndependent growthEnhanced growthEnhanced proliferationReplicativeRegulator
2009
POSH Stimulates the Ubiquitination and the Clathrin-independent Endocytosis of ROMK1 Channels*
Lin DH, Yue P, Pan CY, Sun P, Zhang X, Han Z, Roos M, Caplan M, Giebisch G, Wang WH. POSH Stimulates the Ubiquitination and the Clathrin-independent Endocytosis of ROMK1 Channels*. Journal Of Biological Chemistry 2009, 284: 29614-29624. PMID: 19710010, PMCID: PMC2785594, DOI: 10.1074/jbc.m109.041582.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsBiological TransportCell LineClathrinDynaminsEpithelial Sodium ChannelsGene Expression RegulationHumansKidney Tubules, CollectingOocytesPotassium Channels, Inwardly RectifyingProtein Sorting SignalsProtein Structure, TertiaryRatsRats, Sprague-DawleyUbiquitinationUbiquitin-Protein LigasesXenopus laevisConceptsHEK293T cellsClathrin-independent endocytosisE3 ubiquitin ligaseUbiquitin ligaseGlutathione S-transferase pulldown experimentsROMK1 channelsT cellsTyrosine-based internalization signalPotassium currentROMK channelsDominant-negative dynaminImmunoprecipitation of lysatesInternalization signalInhibitory effectPulldown experimentsScaffold proteinUbiquitination assaysRING domainUbiquitinationN-terminusGamma subunitsAmino acidsENaC-alphaROMK1Tissue lysatesEndothelial and Smooth Muscle-derived Neuropilin-like Protein Regulates Platelet-derived Growth Factor Signaling in Human Vascular Smooth Muscle Cells by Modulating Receptor Ubiquitination*
Guo X, Nie L, Esmailzadeh L, Zhang J, Bender JR, Sadeghi MM. Endothelial and Smooth Muscle-derived Neuropilin-like Protein Regulates Platelet-derived Growth Factor Signaling in Human Vascular Smooth Muscle Cells by Modulating Receptor Ubiquitination*. Journal Of Biological Chemistry 2009, 284: 29376-29382. PMID: 19696027, PMCID: PMC2785569, DOI: 10.1074/jbc.m109.049684.Peer-Reviewed Original ResearchMeSH KeywordsCells, CulturedDown-RegulationHumansMembrane ProteinsMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Muscle, Smooth, VascularMyocytes, Smooth MusclePhosphorylationPlatelet-Derived Growth FactorProto-Oncogene Proteins c-cblReceptor, Platelet-Derived Growth Factor betaSignal Transductionsrc-Family KinasesUbiquitinationUbiquitin-Protein LigasesConceptsPlatelet-derived growth factorSmooth muscle cell-derived neuropilin-like proteinPDGF receptorPlatelet-derived growth factor signalingPrototypic growth factorsE3 ubiquitin ligaseGrowth factor signalingExpression levelsPrimary human VSMCsHuman vascular smooth muscle cellsVascular smooth muscle cell growthReceptor ubiquitinationGrowth factorUbiquitin ligaseFactor signalingRNA interferenceC-CblVascular smooth muscle cellsSmooth muscle cell growthMuscle cell growthVSMC DNA synthesisUbiquitinationESDNHuman VSMCsSmooth muscle cellsThe E3 ubiquitin ligase specificity subunit ASB2β is a novel regulator of muscle differentiation that targets filamin B to proteasomal degradation
Bello NF, Lamsoul I, Heuzé ML, Métais A, Moreaux G, Calderwood DA, Duprez D, Moog-Lutz C, Lutz PG. The E3 ubiquitin ligase specificity subunit ASB2β is a novel regulator of muscle differentiation that targets filamin B to proteasomal degradation. Cell Death & Differentiation 2009, 16: 921-932. PMID: 19300455, PMCID: PMC2709956, DOI: 10.1038/cdd.2009.27.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsCarrier ProteinsCell DifferentiationCell LineChickensContractile ProteinsFilaminsGene Knockdown TechniquesHumansMiceMicrofilament ProteinsMyoblastsProteasome Endopeptidase ComplexRNA InterferenceRNA, MessengerSuppressor of Cytokine Signaling ProteinsUbiquitin-Protein LigasesConceptsFilamin BMuscle differentiationSpecificity subunitAnkyrin repeat-containing proteinActive E3 ubiquitin ligaseE3 ubiquitin ligase complexRepeat-containing proteinUbiquitin ligase complexE3 ubiquitin ligaseSuppressor of cytokineBox 2 geneLigase complexE3 ubiquitinUbiquitin ligaseProteasomal degradationMyoblast fusionNovel regulatorMuscle developmentKnockdown cellsProtein degradationMyogenic differentiationAdult tissuesC2C12 cellsMuscle contractile proteinsInduced differentiation
2007
Increased Expression of the E3 Ubiquitin Ligase RNF5 Is Associated with Decreased Survival in Breast Cancer
Bromberg KD, Kluger HM, Delaunay A, Abbas S, DiVito KA, Krajewski S, Ronai Z. Increased Expression of the E3 Ubiquitin Ligase RNF5 Is Associated with Decreased Survival in Breast Cancer. Cancer Research 2007, 67: 8172-8179. PMID: 17804730, PMCID: PMC2962863, DOI: 10.1158/0008-5472.can-07-0045.Peer-Reviewed Original ResearchConceptsRNF5 expressionBreast cancer cellsCell linesUbiquitin E3 ligasesE3 ubiquitin ligaseMutant breast cancer cellsEndoplasmic reticulum stress responseP53-dependent functionsTumor-derived cell linesCancer cellsImportant regulatory roleReticulum stress responseP53-mutant breast cancer cellsMetastatic melanoma specimensActin cytoskeletal alterationsActin cytoskeletonE3 ligasesHuman breast cancer specimensSelective ubiquitinationUbiquitin ligaseNovel regulatorPaclitaxel-induced apoptosisRelated cell linesBreast cancer progressionStress responseCharacterization of a Novel Cullin5 Binding Domain in HIV-1 Vif
Xiao Z, Xiong Y, Zhang W, Tan L, Ehrlich E, Guo D, Yu X. Characterization of a Novel Cullin5 Binding Domain in HIV-1 Vif. Journal Of Molecular Biology 2007, 373: 541-550. PMID: 17869271, DOI: 10.1016/j.jmb.2007.07.029.Peer-Reviewed Original ResearchConceptsVif functionHCCH motifA3GPotential new targetsA3G degradationE3 ubiquitin ligaseUbiquitin-proteasome machineryHIV-1 VifAnti-viral drug developmentBC boxCul5 boxUbiquitin ligaseNovel motifProteasomal degradationCys residuesNew targetsDrug developmentMotifCullin5ResiduesStructural requirementsVif
2006
Zinc chelation inhibits HIV Vif activity and liberates antiviral function of the cytidine deaminase APOBEC3G
Xiao Z, Ehrlich E, Luo K, Xiong Y, Yu X. Zinc chelation inhibits HIV Vif activity and liberates antiviral function of the cytidine deaminase APOBEC3G. The FASEB Journal 2006, 21: 217-222. PMID: 17135358, DOI: 10.1096/fj.06-6773com.Peer-Reviewed Original ResearchConceptsTetrakis (2-pyridylmethyl) ethylenediamineVif functionZinc chelationE3 ubiquitin ligaseCytidine deaminase APOBEC3GCellular antiviral proteinsLentiviral Vif proteinsAPOBEC3G degradationSubstrate receptorHIV-1 VifMembrane-permeable zinc chelatorVif actsUbiquitin ligaseProteasomal degradationNovel drug designAntiviral functionAntiviral proteinVif proteinAntiviral activityVif activityAPOBEC3GAPOBEC3 proteinsNew targetsInfectivity assaysZinc chelator
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